The proposed studies will define the role of glucagon in modulating the conversion of free fatty acids to ketone bodies. Specifically, the contribution that glucagon makes to the ketogenic action of norepinephrine in vivo will be assessed in both normal and diabetic man. Furthermore, in normal man, the interrelationships of norepinephrine, glucagon, and insulin in modulating the hepatic conversion of free fatty acids to ketone bodies and triglycerides will be defined. Animal studies (rats) will also be performed to define the cellular site of glucagon on modulating free fatty acid metabolism in the liver. This will be done by utilizing the blocking action of two pharmacological agents, (plus) Octanoyl Carnitine and (minus) Carnitine. These two agents which inhibit or enhance the activity of long chain acyl carnitine transferase respectively, will define the action of glucagon at the site of the mitochondrial membrane. These proposed studies will extend our knowledge of the metabolic control of hepatic ketogenesis and give insight into potential regulatory sites which may suggest specific treatment for pathological states of ketoacid excess in diabetic man.